Methods and compositions for treating conditions associated with an abnormal inflammatory response

Abstract

This disclosure features chemical entities (e.g., a compound exhibiting activity as a mitochondrial uncoupling agent or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof, e.g., a compound, such as niclosamide or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof, e.g., a compound, such as a niclosamide analog, or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof) that are useful, e.g., for treating one or more symptoms of a pathology characterized by an abnormal inflammatory response (e.g., inflammatory bowel diseases) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same.

What is claimed is: 
     
       1. A method for treating iatrogenic autoimmune colitis in a subject in need thereof, the method comprising administering an effective amount of a niclosamide wherein the iatrogenic autoimmune colitis is induced by an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor targets CTLA-4. 
     
     
       2. The method of  claim 1 , wherein the immune checkpoint inhibitor is an antibody. 
     
     
       3. The method of  claim 2 , wherein the antibody is ipilimumab or tremelimumab. 
     
     
       4. The method of  claim 2 , wherein the antibody is ipilimumab. 
     
     
       5. The method of  claim 1 , the method comprising administering an effective amount of niclosamide to the GI tract of the subject. 
     
     
       6. The method of  claim 1 , the method comprising, wherein the method comprises locally administering an effective amount of niclosamide to the subject to the GI tract of the subject. 
     
     
       7. The method of  claim 1 , wherein the method comprises topically administering an effective amount of niclosamide to the subject to the GI tract of the subject. 
     
     
       8. The method of  claim 1 , wherein the niclosamide is administered by rectal administration. 
     
     
       9. The method of  claim 8 , wherein the niclosamide is administered by enema, rectal gel, rectal foam, rectal aerosol, or suppository. 
     
     
       10. The method of  claim 8 , wherein the niclosamide is administered by enema. 
     
     
       11. The method of  claim 1 , wherein the niclosamide is administered by oral administration. 
     
     
       12. The method of  claim 11  is administered by tablet or pill. 
     
     
       13. The method of  claim 1 , wherein upon administration, the concentration of the niclosamide in the GI tract is higher than the concentration of the mitochondrial uncoupling agent in the plasma compartment. 
     
     
       14. The method of  claim 1 , wherein the niclosamide in the plasma compartment is subject to first pass metabolism. 
     
     
       15. The method of  claim 6 , wherein upon administration, the concentration of the niclosamide in the GI tract is about 5 times higher than the concentration of the niclosamide in the plasma compartment. 
     
     
       16. The method of  claim 1 , wherein upon administration, the concentration of the niclosamide in the colon is higher than the concentration of the niclosamide in the plasma compartment. 
     
     
       17. The method of  claim 1 , wherein upon administration, the concentration of the niclosamide in the colon is about 5 times higher than the concentration of the niclosamide in the plasma compartment. 
     
     
       18. The method of  claim 1 , wherein upon administration, the concentration of the niclosamide in the rectal mucosa is higher than the concentration of the niclosamide in the plasma compartment. 
     
     
       19. The method of  claim 1 , wherein upon administration, the concentration of the niclosamide in the rectal mucosa is about 5 times higher than the concentration of the niclosamide in the plasma compartment. 
     
     
       20. The method of  claim 1 , wherein the subject is a human.